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1.
J Vet Diagn Invest ; : 1040638720905314, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32065061

RESUMO

Clostridium botulinum is an important pathogen that causes botulism in humans and animals worldwide. C. botulinum group III strains, which produce a single toxin of type C or D or a chimeric toxin of type C/D or D/C, are responsible for botulism in a wide range of animal species including cattle and birds. We used unbiased high-throughput RNA sequencing (i.e., metatranscriptomics) to identify a strain of group III C. botulinum from a deceased Mongolian wild ass (Equus hemionus). The strain was closely related to some European strains. Genetic analysis of the recovered bacterial sequences showed that the C. botulinum strain identified might represent a type C/D strain of group III. Infection by C. botulinum producing the mosaic toxin of type C/D is the most likely cause of the death of the wild ass.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32083455

RESUMO

Currently available strategies show limited effects on preventing morbidity and disability from chronic diabetic wounds. Ideal vascularization is indispensable to better restoration and prognosis of diabetic wound. This study aims to investigate the role of tetrahedral framework nucleic acids (tFNAs) in the process of angiogenesis during diabetic wound healing and the underlying mechanism. The in vitro results showed that tFNAs treatment enhanced the formation of vessel-like structure that was inhibited by advanced glycation end products (AGEs). Positive variations were detected in aspects of cell viability, migratory ability, nitric oxide (NO) level and vascular endothelial growth factor-A (VEGF-A) expression. In addition, high reactive oxygen species (ROS) level and gene expressions relevant to oxidative damage and inflammation in diabetic HUVECs were attenuated by tFNAs. As for the underlying mechanism, p-Akt/total-Akt ratio, nuclear factor erythroid 2-related factor 2 (Nrf2) level and heme oxygenase-1 (HO-1) level were higher in diabetic HUVECs treated with tFNAs. In vivo experiments showed that tFNAs facilitated diabetic wound healing by accelerating vascularization, epithelialization, collagen deposition and collagen alignment. In conclusion, tFNAs could protect endothelial cell function, reduce inflammation and impede oxidative damage through their antioxidant activity via the Akt/Nrf2/HO-1 signaling pathway. The application of tFNAs may pave the way for better healing of diabetic wound.

4.
Cell Prolif ; 53(1): e12708, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31642557

RESUMO

OBJECTIVES: Due to the instability of microRNAs, the applications of microRNA are currently limited. Thus, we utilized tetrahedral framework nucleic acids and a targeted microRNAs to form a stable nanocomposite to explore whether this nanocomposite can promote apoptosis of tumour cells. MATERIALS AND METHODS: In our study, the survivin gene, which is expressed only in tumour cells and embryonic cells, was selected as the target gene; miRNA-214-3p, which can reduce the expression of survivin, was modified onto tetrahedral framework nucleic acid, thereby producing a reduction in the expression of survivin upon intracellular delivery and eventually leading to tumour cell apoptosis. RESULTS: By comparing the stability of microRNAs with that of microRNA-tetrahedral framework nucleic acid, we proved the superiority of this carrier system. The results of flow cytometry showed that after treated with this complex, the ratio of A549 cells in both late and early period of apoptosis in miRNA-214-3p-tetrahedral framework nucleic acid group had doubled and the cell cycle in the G2-M phase had declined. The decrease in the expression of anti-apoptotic protein and the increase in the expression of pro-apoptotic protein indicate that the ability of this complex to function in cells also makes it attractive as a new targeted therapy for cancer. CONCLUSION: The unique expression of survivin in tumour cells and embryonic cells makes microRNA-tetrahedral framework nucleic acid a new targeted therapy. In addition, due to the functional diversity of microRNAs, this delivery system approach can be applied to a wide variety of fields, such as targeted therapy and tissue regeneration.

5.
Int J Cancer ; 146(7): 2027-2035, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693169

RESUMO

The heterogeneities of colorectal cancer (CRC) lead to staging inadequately of patients' prognosis. Here, we performed a prognostic analysis based on the tumor mutational profile and explored the characteristics of the high-risk tumors. We sequenced 338 colorectal carcinomas as the training dataset, constructed a novel five-gene (SMAD4, MUC16, COL6A3, FLG and LRP1B) prognostic signature, and validated it in an independent dataset from The Cancer Genome Atlas (TCGA). Kaplan-Meier and Cox regression analyses confirmed that the five-gene signature is an independent predictor of recurrence and prognosis in patients with Stage III colon cancer. The mutant signature translated to an increased risk of death (hazard ratio = 2.45, 95% confidence interval = 1.15-5.22, p = 0.016 in our dataset; hazard ratio = 4.78, 95% confidence interval = 1.33-17.16, p = 0.008 in TCGA dataset). RNA and bacterial 16S rRNA sequencing of high-risk tumors indicated that mutations of the five-gene signature may lead to intestinal barrier integrity, translocation of gut bacteria and deregulation of immune response and extracellular related genes. The high-risk tumors overexpressed IL23A and IL1RN genes and enriched with cancer-related bacteria (Bacteroides fragilis,Peptostreptococcus, Parvimonas, Alloprevotella and Gemella) compared to the low-risk tumors. The signature identified the high-risk group characterized by gut bacterial translocation and upregulation of interleukins of the tumor microenvironment, which was worth further researching.

6.
Dis Markers ; 2019: 1761693, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871497

RESUMO

Gene-environment interaction is identified as the determinant in anxiety. ABO blood types represent a part of the genetic phenotype. Therefore, we assume ABO blood types correlate with preoperative anxiety. This cross-sectional study enrolled 352 patients with different ABO blood types, scheduled for elective surgery between 2018 and 2019 in the First Affiliated Hospital of Shihezi University. HADS (hospital anxiety and depression scale) scores and VA (visual analogue scales for anxiety) scores were all used to assess the preoperative anxiety in the A, B, AB, and O groups. Bivariate correlation and logistic regression were performed to identify relationships between preoperative anxiety and related variables. A significant difference in VA and HADS-A (anxiety) scores was found between the AB and other groups. The ratio of preoperative anxiety was 3.73 (95% CI [confidence interval]: 2.32-6.00, P < 0.001) times in female than in male; 0.36 (95% CI: 0.21-0.63, P < 0.001) times in ASA (American Society of Anesthesiologists) grade II than in grade I; 0.41 (95% CI: 0.20-0.86, P < 0.05) times in ASA grade III than in grade I; 1.25 (95% CI: 1.1-1.41, P < 0.001) times in higher VAS (visual analogue scales for pain) scores than in lower VAS scores; and 0.28 (95% CI: 0.16-0.49, P < 0.01) times in non-AB blood type than in AB blood type. Differences in ABO blood types were found in preoperative anxiety, and the AB group displayed a high preoperative anxiety level. ABO blood types, sex, ASA grade, and VAS were associated with preoperative anxiety. This trial is registered with ChiCTR1800019390.

7.
J Appl Psychol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670527

RESUMO

Extant research has uniformly demonstrated that leader humility is beneficial for subordinates, teams, and even organizations. Drawing upon attribution theory, we challenge this prevailing conclusion by identifying a potential dark side of leader humility and suggesting that leader humility can be a mixed blessing. We propose that the effects of leader humility hinge on subordinates' attributions of such humble behavior. On the one hand, when subordinates attribute leader humility in a self-serving way, leader humility is positively associated with subordinate psychological entitlement, which in turn increases workplace deviance. On the other hand, when subordinates do not attribute leader humility in a self-serving way, leader humility is positively associated with leader-member exchange, which in turn decreases workplace deviance. We found support for our hypotheses across a field study and an experiment. Taken together, our findings reveal the perils and benefits of leader humility and the importance of examining subordinate attributions in this unique leadership process. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

8.
Br J Pharmacol ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734944

RESUMO

BACKGROUND AND PURPOSE: Lipid metabolism disorder and disturbed mitochondrial bioenergetics play pivotal roles in the occurrence and development of diabetic kidney disease (DKD). Berberine (BBR) is a kind of alkaloid derived from Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity and alleviation of oxidative damage. Here we investigated the renoprotective effects of BBR. EXPERIMENTAL APPROACH: Combined clinical study in DKD patients with experimental studies in diabetic mice and cultured podocytes, we characterized the energy metabolism profiles based on metabolomics, investigated molecular targets and mechanisms of BBR at regulating mitochondrial function and bioenergetics, and testified the effects of BBR on metabolic alterations in DKD animal model. KEY RESULTS: Metabolomics examination suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in DKD patients. BBR intervention potently reversed metabolic disorders, podocyte damage and glomerulosclerosis in db/db mice. Lipid accumulation, excessive generation of mitochondrial reactive oxygen species, mitochondrial dysfunction and insufficient fatty acids oxidation in DKD mouse models and cultured podocytes were significantly suppressed by BBR. The protective mechanism of BBR might involve the activation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling pathway, thereby promoting mitochondrial energy homeostasis and fatty acid oxidation in podocytes. CONCLUSION AND IMPLICATIONS: Our research elucidated that PGC-1α-mediated mitochondrial bioenergetics might play a key role in lipid disorder-induced podocyte damage and development of DKD. Restoration of PGC-1α activity and the energy homeostasis by BBR might be a potential therapeutic strategy against DKD.

9.
BMC Gastroenterol ; 19(1): 188, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729975

RESUMO

BACKGROUND: The aim of this study was to explore the prognostic factors and establish a nomogram to predict the long-term survival of gastric cancer patients. METHODS: The clinicopathological data of 421 gastric cancer patients, who were treated with radical D2 lymphadenectomy by the same surgical team between January 2009 and March 2017, were collected. The analysis of long-term survival was performed using Cox regression analysis. Based on the multivariate analysis results, a prognostic nomogram was formulated to predict the 5-year survival rate probability. RESULTS: In the present study, the total overall 3-year and 5-year survival rates were 58.7 and 45.8%, respectively. The results of the univariate Cox regression analysis revealed that tumor staging, tumor location, Borrmann type, the number of lymph nodes dissected, the number of lymph node metastases, positive lymph nodes ratio, lymphocyte count, serum albumin, CEA, CA153, CA199, BMI, tumor size, nerve invasion, and vascular invasion were prognostic factors for gastric cancer (all, P < 0.05). However, merely tumor staging, tumor location, positive lymph node ratio, CA199, BMI, tumor size, nerve invasion, and vascular invasion were independent risk factors, based on the results of the multivariate Cox regression analysis (all, P < 0.05). The nomogram based on eight independent prognostic factors revealed a well-degree of differentiation with a concordance index of 0.76 (95% CI: 0.72-0.79, P < 0.001), which was better than the AJCC-7 staging system (concordance index = 0.68). CONCLUSION: The present study established a nomogram based on eight independent prognostic factors to predict long-term survival in gastric cancer patients. The nomogram would be beneficial for more accurately predicting the prognosis of gastric cancer, and provide important basis for making individualized treatment plans following surgery.

10.
BMC Complement Altern Med ; 19(1): 314, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744490

RESUMO

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80+ ratio and CD11c+ ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80+CD11c+ M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.


Assuntos
Berberina/farmacologia , Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Berberina/química , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/química , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Fator 88 de Diferenciação Mieloide/química , Fator 88 de Diferenciação Mieloide/genética , Ligação Proteica/efeitos dos fármacos , Células RAW 264.7 , Receptor 4 Toll-Like/química , Receptor 4 Toll-Like/genética , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Nanoscale ; 11(43): 20667-20675, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31642452

RESUMO

Retinal ischemia-reperfusion (I/R) injuries are involved in the universal pathological processes of many ophthalmic diseases, including glaucoma, diabetic retinopathy, and retinal arterial occlusion. The reason is that the ischemia-reperfusion injury is accompanied by the abnormal accumulation of reactive oxygen species (ROS), which can cause damage to retinal ganglion cells (RGCs), promote their apoptosis, and finally lead to the irreversible loss of the visual field. RGCs are specialized projection neurons that are situated in the inner retinal surface of the eye, and they transmit visual images into certain areas of the brain in the form of action potentials. Therefore, any damage that affects the viability of RGCs can cause visual field defects or even irreversible vision loss. There is no effective drug treatment in clinical practice for the loss of the visual field that is caused by the oxidation and apoptosis of RGCs. Hence, finding a drug with neuroprotective and antioxidant functions is urgently needed. As a new type of nanomaterial, tetrahedral framework nucleic acids (tFNAs) exhibit outstanding biocompatibility and have been shown in our previous studies to participate in the positive regulation of cell behavior. In this experiment, we first established a cellular model of oxidative stress in RGCs with tert-butyl peroxide (TBHP). Then, we primarily explored the antioxidant and neuroprotective effects of tFNAs after TBHP-induced oxidative stress and the main mechanisms by which the tFNAs function. Our research showed that tFNAs could reduce the production of reactive oxygen species (ROS) in cells and protect the cells from oxidative stress by regulating intracellular oxidation-related enzymes. In addition, tFNAs could simultaneously improve oxidative stress-induced apoptosis significantly via affecting the expression of apoptosis-related proteins. Finally, we confirmed by western blotting that the mechanism by which tFNAs prevent damage caused by oxidative stress involves activating the Akt/Nrf2 pathway. Our findings provide new ideas for the prevention and treatment of a series of diseases that are caused by oxidative stress to RGCs.

12.
Eur J Radiol ; 120: 108686, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31586850

RESUMO

PURPOSE: To determine whether imaging parameters derived from intravoxel incoherent motion (IVIM) diffusion weighted imaging (DWI) vary according to tumor-stroma ratio(TSR) or dominant stroma type of breast cancer. METHODS: We prospectively enrolled 77 patients with breast cancer who underwent IVIM DWI on a 3.0 T MR scanner. The values of IVIM parameters (D, D* and f) were measured. After surgery, TSR or dominant stroma type was evaluated. The relationship between imaging parameters and tumor stroma characteristics was analyzed. RESULTS: The mean D and f values were lower in stroma-poor tumor than in stroma-rich tumor (P = 0.012, 0.015). The mean D value was lower in the collagen-dominant type than in fibroblast-dominant or lymphocyte-dominant type (P = 0.032, 0.043). According to multivariate linear regression analyses, tumor size (P = 0.007), TSR (P = 0.008), dominant stroma type (collagen dominant, P = 0.012), and histological grade (P = 0.031) were independently correlated with D value; and tumor size (P = 0.011), TSR (P = 0.021) and histological grade (P = 0.037) were independently correlated with f value. CONCLUSION: In breast cancer, D and f values show significant differences according to TSR, and D value is lower in collagen dominant type than in fibroblast dominant or lymphocyte dominant types.

13.
Sensors (Basel) ; 19(18)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546817

RESUMO

Deep learning (DL) is a powerful technique which has achieved great success in many applications. However, its usage in communication systems has not been well explored. This paper investigates algorithms for multi-signals detection and modulation classification, which are significant in many communication systems. In this work, a DL framework for multi-signals detection and modulation recognition is proposed. Compared to some existing methods, the signal modulation format, center frequency, and start-stop time can be obtained from the proposed scheme. Furthermore, two types of networks are built: (1) Single shot multibox detector (SSD) networks for signal detection and (2) multi-inputs convolutional neural networks (CNNs) for modulation recognition. Additionally, the importance of signal representation to different tasks is investigated. Experimental results demonstrate that the DL framework is capable of detecting and recognizing signals. And compared to the traditional methods and other deep network techniques, the current built DL framework can achieve better performance.

14.
Front Neurol ; 10: 808, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447754

RESUMO

Background: Cerebral small vessel disease (SVD) is generally considered as a cause of stroke, disability, gait disturbances, vascular cognitive impairment, and dementia. The aim of this study was to investigate whether the total SVD burden can be used to predict functional outcome in patients with acute ischemic stroke. Methods: From April 2017 to January 2018, consecutive patients with acute ischemic stroke who underwent baseline MRI scan were evaluated. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days and defined as i) excellent outcome (mRS ≤ 1) and ii) good outcome (mRS ≤ 2). Brain MRI was performed and assessed for lacunes, white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The total SVD burden was calculated based on lacunes, WMH, and EPVS and then summed up to generate an ordinal "total SVD burden" (range 0-3). Bivariate logistic regression models were used to identify the association between SVD and functional outcome. Results: A total of 416 patients were included in the final analysis; 44.0, 33.4, 19.2, and 3.4% of the patients had 0, 1, 2, and 3 features of SVD, respectively. In regard to individual SVD feature, lacunes (OR: 0.48, 95% CI: 0.32-0.71; OR: 0.49, 95% CI: 0.31-0.77) and WMH (OR: 0.53, 95% CI: 0.34-0.82; OR: 0.53, 95% CI: 0.33-0.85) were negatively associated with excellent outcome and good outcome. As to the total burden of SVD, three SVD features had strongest negative associations with functional outcomes (excellent outcome, OR: 0.13, 95% CI: 0.03-0.48; good outcome, OR: 0.18, 95% CI: 0.06-0.54). After adjustment for potential confounders, a high SVD burden (3 features, OR: 0.07, 95% CI: 0.01-0.41) and the score of total SVD burden (OR: 0.64, 95% CI: 0.44-0.93) remained negatively associated with excellent outcome. Conclusion: Total SVD burden negatively associated with functional outcome at 3 months in patients with acute ischemic stroke and is superior to individual SVD feature in prediction of functional outcome. MRI-based assessment of total SVD burden is highly valuable in clinical management of stroke victims and could help guide the allocation of resources to improve outcome.

15.
ACS Appl Mater Interfaces ; 11(36): 32787-32797, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31424187

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease characterized by a series of progressive motor disorders. PD is caused by dysfunction of basal ganglia, decrease of dopaminergic neurons in substantia nigra, and abnormal accumulation of Lewy bodies and Lewy neurites. Antiparkinsonian agents, which are currently used for treatment of PD, exhibit unsatisfactory effects on disease control. In recent years, tetrahedral framework nucleic acids (TFNAs) have been considered as multifunctional nanomaterials, and their scope of application has been extended to a wide range of areas. In previous studies, TFNAs were shown to exert positive effects on various cell types in processes such as cell proliferation, cell differentiation, and apoptosis. In the present study, we explored the role of TFNAs in the treatment and prevention of PD in vitro and elucidated its underlying mechanisms of action. On the basis of the experiments conducted, we demonstrated that TFNAs could inhibit and repair the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of PC12 cells through decreasing the accumulation of α-synuclein, one of the characteristic biomarkers of PD. Genes and proteins related to the AKT/PI3K signaling and mitochondrial apoptotic pathways were examined to further support this finding. Most importantly, TFNAs exhibited unexpected neuroprotective and neurorestorative effects on PC12 cells, providing a novel approach for reducing the neuropathological changes caused by PD.

16.
ACS Appl Mater Interfaces ; 11(34): 30631-30639, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31382735

RESUMO

Acute myocardial infarction, which can be extremely difficult to treat, is the worst deadly disease around the world. Reperfusion is expedient to reverse myocardial ischemia. However, during reperfusion, reactive oxygen species (ROS) produced by myocardial ischemia-reperfusion injury (MIRI) and further cell apoptosis are the most serious challenges to cardiomyocytes. Therefore, searching for reagents that can simultaneously reduce oxidative damage and MIRI-induced apoptosis is the pivotal strategy to rescue injured cardiomyocytes. Nevertheless, current cardioprotective drugs have some shortcomings, such as cardiotoxicity, inadequate intravenous administration, or immature technology. Previous studies have shown that tetrahedral DNA nanostructures (TDNs) have biological safety with promising anti-inflammatory and antioxidative potential. However, the progress that TDNs have made in the biological behavior of cardiomyocytes has not been explored. In this experiment, a cellular model of MIRI was first established. Then, confirmed by a series of experiments, our study indicates that TDNs can significantly decrease oxidative damage and apoptosis by limiting the overexpression of ROS, along with effecting the expression of apoptosis-related proteins. In addition, Western blot analysis demonstrated that TDNs could activate the Akt/Nrf2 signaling pathway to improve the myocardial injury induced by MIRI. Above all, the antioxidant and antiapoptotic capacities of TDNs make them a potential therapeutic drug for MIRI. This study provides new ideas and directions for more homogeneous diseases induced by oxidative damage.


Assuntos
Cardiotônicos , DNA , Depuradores de Radicais Livres , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Nanoestruturas/química , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/química , Cardiotônicos/farmacologia , Linhagem Celular , DNA/química , DNA/farmacologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Oncol Rep ; 42(2): 615-628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233188

RESUMO

FK506 binding protein 10 (FKBP10) has been reported to be dysregulated in numerous types of cancer; however, few reports have investigated FKBP10 in gastric cancer (GC). The aim of the present study was to investigate FKBP10 expression in GC and to analyze its association with the prognosis of patients with GC. FKBP10 mRNA expression was evaluated using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The standardized mean differences of the meta­analysis were comprehensively evaluated for FKBP10 expression from a series of GEO datasets. Kaplan­Meier survival and Cox regression analyses were applied to predict the prognostic value of FKBP10 in patients with GC. Additionally, the protein expression levels of FKBP10 were validated by immunohistochemistry (IHC) in 40 GC and adjacent tissues. FKBP10 co­expression network and bioinformatics analyses were then used to explore the potential functional mechanisms of FKBP10. The results revealed that the mRNA expression levels of FKBP10 were significantly increased in GC within the TCGA and GEO databases. Survival analysis revealed that high FKBP10 expression results in poorer overall survival and disease­free survival (P<0.05). Multivariate cox regression analysis indicate FKBP10 as a dependent prognostic factor. The results of IHC indicated that the protein expression levels of FKBP10 were higher in GC tissues than in adjacent non­GC tissues (P<0.001). Co­expression networks and functional enrichment analysis suggested that FKBP10 may be involved in the development of GC via cell adhesion molecules and extracellular matrix­receptor interaction pathways. Therefore, the findings of the present study indicated that FKBP10 is upregulated in GC tissues, and suggests its potential prognostic value. Therefore FKBP10 may be a potential therapeutic target for the treatment of GC.


Assuntos
Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas de Ligação a Tacrolimo/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Neoplasias Gástricas/genética , Taxa de Sobrevida , Proteínas de Ligação a Tacrolimo/genética
18.
Adv Nutr ; 10(5): 791-802, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31212316

RESUMO

Dyslipidemia is a global health problem and a high risk factor for atherosclerosis, which can lead to serious cardiovascular disease (CVD). Existing studies have shown inconsistent effects of turmeric and curcuminoids on blood lipids in adults. We performed this systematic review and meta-analysis to evaluate the effects of turmeric and curcuminoids on blood triglycerides (TG), total cholesterol (TC), LDL cholesterol, and HDL cholesterol. We searched the English databases of the Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, and the Cochrane Library and 2 Chinese databases, Wanfang Data and China National Knowledge Infrastructure, for randomized controlled trials (RCTs) that studied the effects of turmeric and curcuminoids on blood TG, TC, LDL cholesterol, and HDL cholesterol in subjects with metabolic diseases. With random-effects models, separate meta-analyses were conducted by using inverse-variance. The results are presented as the mean difference with 95% CIs. Evidence from 12 RCTs for TG, 14 RCTs for TC, 13 RCTs for LDL cholesterol, and 16 RCTs for HDL cholesterol showed that turmeric and curcuminoids could lower blood TG by -19.1 mg/dL (95% CI: -31.7, -6.46 mg/dL; P = 0.003), TC by -11.4 mg/dL (95% CI: -17.1, -5.74 mg/dL; P < 0.0001), and LDL cholesterol by -9.83 mg/dL (95% CI: -15.9, -3.74 mg/dL; P = 0.002), and increase HDL cholesterol by 1.9 mg/dL (95% CI: 0.31, 3.49 mg/dL; P = 0.02). In conclusion, turmeric and curcuminoids can significantly modulate blood lipids in adults with metabolic diseases. However, these findings should be interpreted cautiously because of the significant heterogeneity between included studies (I2 > 50%). There is a need for further RCTs in future.

19.
World J Gastrointest Oncol ; 11(6): 499-508, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31236200

RESUMO

BACKGROUND: Radical D2 lymphadenectomy for advanced gastric cancer as a standard procedure has gained global consensus. Mounting studies have shown that the number of lymph nodes dissection directly affects the prognosis and recurrence of gastric cancer. Our previous study showed that there was no obvious lymph node around the abnormal hepatic artery derived from the superior mesenteric artery. AIM: To investigate the relationship between celiac artery variation and the number of lymph nodes dissection in gastric cancer surgery. METHODS: The clinicopathological data of 421 patients treated with radical D2 lymphadenectomy were analyzed retrospectively. The difference of the number of lymph nodes dissection between the celiac artery variation group and the normal vessels group and the relationship with prognosis were analyzed. RESULTS: Celiac artery variation was found in 110 patients, with a variation rate of 26.13%. Celiac artery variation, tumor staging, and Borrmann typing were factors that affected lymph node clearance in gastric cancer, and the number of lymph nodes dissection in patients with celiac artery variation was significantly less than that of non-variant groups (P < 0.05). Univariate analysis showed that there was no significant difference in survival time between the two groups (P > 0.05). Univariate and multiple Cox regression analysis showed that celiac artery variation was not a prognostic factor for gastric cancer (P > 0.05). Tumor staging, intraoperative bleeding, and positive lymph node ratio were prognostic factors for gastric cancer patients (all P < 0.05). CONCLUSION: The number of lymph nodes dissection in patients with celiac artery variation was reduced, but there was no obvious effect on prognosis. Therefore, lymph nodes around the abnormal hepatic artery may not need to be dissected in radical D2 lymphadenectomy.

20.
Theranostics ; 9(6): 1698-1713, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037132

RESUMO

Elevated levels of plasma free fatty acid (FFA) and disturbed mitochondrial dynamics play crucial roles in the pathogenesis of diabetic kidney disease (DKD). However, the mechanisms by which FFA leads to mitochondrial damage in glomerular podocytes of DKD and the effects of Berberine (BBR) on podocytes are not fully understood. Methods: Using the db/db diabetic mice model and cultured mouse podocytes, we investigated the molecular mechanism of FFA-induced disturbance of mitochondrial dynamics in podocytes and testified the effects of BBR on regulating mitochondrial dysfunction, podocyte apoptosis and glomerulopathy in the progression of DKD. Results: Intragastric administration of BBR for 8 weeks in db/db mice significantly reversed glucose and lipid metabolism disorders, podocyte damage, basement membrane thickening, mesangial expansion and glomerulosclerosis. BBR strongly inhibited podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation and dysfunction both in vivo and in vitro. Mechanistically, BBR could stabilize mitochondrial morphology in podocytes via abolishing palmitic acid (PA)-induced activation of dynamin-related protein 1 (Drp1). Conclusions: Our study demonstrated for the first time that BBR may have a previously unrecognized role in protecting glomerulus and podocytes via positively regulating Drp1-mediated mitochondrial dynamics. It might serve as a novel therapeutic drug for the treatment of DKD.

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